Cyclopropenylium salts

ABSTRACT

1. A COMPOUND HAVING THE FORMULA   1-R1,2-R2,3-R3-CYCLOPROPENYLIUM X(-)   WHERE R1 AND R2 ARE EACH T-BUTYL OR 1-ADAMANTYL; R3 IS 1ADAMANTYL-LOWER-ALKYL, PHENYL OR 1-ADAMANTYL; X- IS TETRAFLUOROBORATE, AND WHERE R3 AS PHENYL IS EITHER UNSUBSTITUTED OR IS SUBSTITUTED BY FROM ONE TO THREE LOWERALKYLS.

United States Patent Office 3,839,460 CYCLOPROPENYLIUM SALTS John W. Schulenherg, Bethlehem, N.Y., assignor to Sterling Drug Inc, New York, N.Y.

No Drawing. Original application Aug. 10, 1970, Ser. No. 62,618, now Patent No. 3,728,388. Divided and this application Aug. 16, 1972, Ser. No. 281,206

Int. Cl. C07f /02 US. Cl. 260-6065 B 4 Claims ABSTRACT OF THE DISCLOSURE l,2,3-trisubstituted-cyclopropenylium salts having antibacterial and antiviral activity and prepared either by reaction of a 2,3-disubstituted-cyclopropenone with a trialkyloxonium tetrafluoroborate followed by reaction of the resulting l-alkoxycyclopropenylium tetrafluoroborate with an amine or by reaction of a 2,3-disubstituted-cyclopropenone with an organo metallic compound followed by treatment of the resulting carbinol with a strong acid.

This application is a division of my prior copending application Ser. No. 62,618, filed Aug. 10, 1970, now Pat. No. 3,728,388.

This invention relates to novel chemical compositions known in the art of chemistry as 1,2,3-trisubstitutedcyclopropenylium salts, and having the formulas:

where R and R are each, i.e. independently of one another, t-hutyl or l-adamantyl; R is l-adamantylloWer-alkyl, phenyl, or l-adamantyl; R and R are each hydrogen or lower-alkyl, or R is hydrogen and R" is lower-alkyl, phenyl, phenyl-lower-alkyl, 1- or 2- adamantyl, Z-benzyloxyethyl, cycloalkyl, carbamyl (NHCONH thiocarbamyl (-NHCSNH or phenylamino, or R is lower-alkyl and R is 1- or 2- adamantyl, or R and R together With the nitrogen atom to which they are attached form a heterocyclic ring selected from the group consisting of l-morpholino and polymethyleneimino having from two to six ring carbon atoms; and X- is an anion of a strong acid.

As used herein the term lower-alkyl means saturated, monovalent aliphatic radicals, including straight or branched-chain radicals, of from one to six carbon atoms, as illustrated by, but not limited to, methyl, ethyl, propyl, isopropyl, butyl, amyl, hexyl, and the like.

As used herein, the term cycloalkyl means saturated carbocyclic groups having from three to seven ring carbon atoms and having up to ten total carbon atoms, as illustrated by, but not limited to, cyclopropyl, Z-methylcyclopropyl, cyclobutyl, cyclohexyl, 3-ethylcyclopentyl, 2,5-dimethylcyclohexyl, and cycloheptyl.

When R and R together with the amino nitrogen atom is polymethyleneimino having from two to six ring carbon atoms, the latter can contain up to a total of ten carbon atoms and thus represents, inter alia, 1- aziridino, Z-methylaziridino, l-azetidino, l-pyrrolidino, lpiperidino, 2,4,G-trimethylpiperidino, or l-hexamethyleneimino.

The anions represented by the group X in the compounds of formulas Ia and lb are in themselves neither novel nor critical, and can be any anion of a strong inorganic or organic acid, such as bromide, chloride, iodide, sulfate, tetrafluoroborate, perchlorate, p-toluenesulfonate, or methanesulfonate.

Moreover in the compounds of formulas Ia and Ib where R or R" include a phenyl-bearing radical, that is where R is phenyl or where R is phenyl, phenyl-loweralkyl, Z-benzyloxyethyl, or phenylamino, the benzene ring of the phenyl-bearing moiety can be unsubstituted or can be substituted by methylenedioxy or ethylenedioxy or by from one to three members of the group consisting of halogen, lower-alkyl, lower-alkoxy, lower-alkylmercapto, or di-lower-alkylamino.

The compounds of formula Ia where X- is the tetrafiuoroborate anion are prepared by reaction of a 2,3- disubstituted-cyclopropenone of formula II with a trilower-alkyloxonium tetrafluoroborate (Meerweins reagent) and treatment of the resulting l-lower-alkoxy-2,3 disubstituted-cyclopropenylium tetrafiuoroborate with an appropriate amine. The method is represented by the equations:

where R R R, and R have the meanings indicated above, and Alk is lower-al kyl. The reaction is carried out in an organic solvent inert under the condition of the reaction, for example methylene dichloride, ethylene dichloride, chlorofonn, and the like, and at temperatures in the range from about 0 C. to about 40 C. The products either precipitate from the reaction medium directly and can be isolated by filtration, or they are caused to preciplitate by dilution of the reaction mixture with diethyl et er.

The compounds of formula Ia where R is hydrogen and R" is carbamyl or thiocarbamyl are prepared by reaction of a 2,3-disubstituted-cyclopropenone of formula II with either semicarbazide or thiosemicarbazide in an organic solvent inert under the conditions of the reaction, preferably a lower-alkanol such as methanol, ethanol, or isopropanol and in the presence of a strong acid, HX, preferably at the boiling point of the solvent.

The compounds of formula Ib are prepared by reaction of a 2,3-disubstituted-cyclopropenone of formula II with an organo lithium compound (R )Li or an organo magnesium halide (R )MgX, followed by treatment of the resulting carbinol with a strong acid (HX) as illustrated by the following equations:

Where R R R and X have the meanings given above. The reaction is carried out at a temperature in the range from about -10 to about 30 C. and in an organic sol vent inert under the conditions of the reaction, for example diethyl ether, tetrahydrofuran, benzene, or mixtures of these solvents.

The 2,3-disubstituted-cyclopropenones of formula III are in turn prepared by reaction of a substituted acetyl halide of the formula R CH COX with an appropriate Grignard reagent of the formula R CH MgCl where R 7 and R have the meanings given above and X is chlorine as 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU) or 1,5-

3 diazabicyclo[4.3.0]non--ene (DBN). The procedure is illustrated by the equations:

0 ll RrCHzCOX RgCHgMgCl RrCHzCCHzR:

Br Br where R R and X have the meanings given above.

The instant invention also contemplates compounds having the formulas III and IV:

III IV where R R and R have the meanings given above, and Me represents an alkali metal. The reaction of the cyclopropenylium salt of formula Ib With the alkali metal cyanide is carried out in an organic solvent, such as acetonitrile, acetone, methanol, ethanol, isopropanol and the like, at the boiling point thereof. The reduction of the carbonitrile is advantageously carried out in diethyl ether or tetrahydrofuran at temperatures from around 0 C. up to the boiling point of the solvent used.

The compounds of formula IV are prepared by reacting a compound of formula II with a benzenesulfonyl isocyanate in an organic solvent inert under the conditions of the reaction, for example, methylene dichloride, chloroform, ethylene dichloride, benzene, and the like.

As indicated above, the acid anion represented by X is not a critical feature of the invention and can be any anion of a strong acid such as those exemplified above. Therefore, if desired a particular salt species may be converted to another species having a different anion by use of various ion exchange procedures, for example by passing a solution of the salt over an appropriate ion exchange column.

The compounds of formulas Ia, Ib, II, III, and IV have been found to possess antibacterial activity, and the compounds of formulas Ia and Ib, in addition, have been found to possess antiviral activity against Asian A variant, Japanese strain of influenza virus and against Influenza Maryland strain virus, thus indicating usefulness of the compounds of formulas Ia and lb as antibacterial and antiviral agents, and the compounds of formulas II, III, and IV as antibacterial agents. The compounds of formula II are of course additionally useful as intermediates for the preparation of the compounds of formulas Ia and lb as described above.

The antibacterial activity was determined using a modification of the Autotiter method described by Goss et al., Applied Microbiology, 16 (No. 9), 1414-1416 (1968) in which a 1000 meg/ml. solution of the test compound is prepared. To the first cup of the Autotray is added 0.1 ml. of the test solution. Activation of the Autotiter initiates a sequence of operations by which 0.05 ml. of the test compound solution is withdrawn from this cup by a Microtiter transfer loop and diluted in 0.05 ml. of sterile semi-synthetic medium (glucose). After this operation, 0.05 ml. of inoculated semi-synthetic medium is added automatically to each cup. The overall operation results in final drug concentrations ranging from 500 to 0.06 meg/ml. in twofold decrements. The Autotray is incubated for 18-20 hours at 37 C., at which time the trays are examined visually for growth as evidenced by turbidity, and the concentration of the last sample in the series showing no growth (or no turbidity) is recorded as the minimal inhibitory concentration (MIC). The compounds of formulas Ia, Ib, II, III, and IV were thus found to be antibacterially effective against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Proteus vulgaris at concentrations from 3.1 to 500 mcg./ml.

The anti-influenza-viral activity of the compounds was determined in mice in a lung inflammation test which is described as follows: Each of a group of ten female Swiss mice weighing 12-15 g. is medicated subcutaneously with the test compound twice daily for five consecutive days. Twenty animals are maintained as non-medicated infected controls and twenty others as normal non-infected controls. On the second day of medication, each animal is infected by intranasal administration of approximately one LD of a strain of influenza virus (maintained as a suspension of infected mouse lung in sterile tryptose phosphate broth) in a volume of 0.05 ml. One LD of influenza virus under the conditions of the experiment produces approximately a two-fold increase in average lung weight. On the sixth day after infection, all animals are anesthetized by intraperitoneal administration of sodium pentobarbital, the animals sacrificed, and the lungs excised and weighed to the nearest milligram. Statistical treatment of differences of lung weight between treated mice and infected non-medicated controls by the Mann-Whitney U Test results in probability values (p value), and the compounds were considered active or inactive according to Whether the p value is .01 or .05, respectively.

In use, the compounds can be formulated by preparing a dilute solution in an aqueous medium or in a solution containing a surfactant, or alternatively in an organic medium in which the compounds are soluble, for example ethyl alcohol, and are applied to a surface to be disinfected by conventional means such as spraying, swabbing immersion, and the like. Alternatively the compounds can be formulated as ointments or creams by incorporating them in conventional ointment or cream bases, for example alkylpolyether alcohols, cetyl alcohol, stearyl alcohol, and the like, or as jellies by incorporating them in conventional jelly bases as glycerol and tragacanth. They can also be formulated for use as aerosol sprays or foams.

The molecular structures of the compounds of my invention were assigned on the basis of study of their infrared, ultraviolet, and NMR spectra, and confirmed by the correspondence between calculated and found values for the elementary analyses for representative examples.

The following examples will further illustrate the invention without, however, limiting it thereto.

EXAMPLE 1 (A) 2,3-di-t-butylcyclopropenone To a mixture of 12 g. (0.50 g. atom) of magnesium turnings in dry ether was added about half of a solution containing 48.2 g. (0.45 mole) of neopentyl chloride in 300ml. of dry ether. The reaction was started by addition of afew drops of ethyl bromide and by crushing the magnesium turnings with a glass rod, and when the reaction had begun, the remaining portion of the neopentyl chloride solution was added in portions over a period of about an hour and a half. The reaction mixture was stirred and refluxed overnight, and then cooled in an ice bath, treated dropwise over a period of about two hours with a solution of 48.6 g. (0.36 mole) of t-butylacetyl chloride in 150 ml. of absolute ether, and then refluxed for an additional two hours, after which it was cooled in an ice bath, treated dropwise with 50 ml. of water, then with 50 ml. of 6N hydrochloric acid, and stirred for fifteen minutes. The organic layer was then separated, the aqueous layer extracted with ether, and the combined organic extracts were dried over magnesium sulfate. Removal of the solvent in vacuo and distillation of the residual yellow oil in vacuo gave 47.0 g. of 2,2,6,6-tetrarnethyl- 4-heptanone, b.p. 7476 C./ 17 mm.; n =1.4181.

The above ketone (0.28 mole), dissolved in 160 ml. of glacial acetic acid in a 500 ml. three necked flask equipped with. a dropping funnel, thermometer, and magnetic stirrer, was treated dropwise over a period of about two hours with a solution of 88.3 g. (0.55 mole) of bromine in 160 ml. of glacial acetic acid, while maintaining the temperature below 41 C. When addition was complete, the mixture was stirred an additional half hour, the excess bromine destroyed by addition of aqueous sodium bisulfite, and the light yellow solution was poured into cold water. The yellowsolid which separated was collected and recrystallized from methanol to give two crops totaling 73.3 g. of 3,5 dibromo-2,2,6,6-tetramethyl-4-heptanone, m.p. 7173 C.

Asolution'of 16.4 g. (0.05 mole) of 3,5-dibromo-2,2, 6,6-tetramethyl-4-heptanone in 50 ml. of chloroform was treated-with'14.9 g. (0.12 mole) of 1,5-diazabicyclo[4.3.0] non-S-ene (DBN), and the reaction mixture was refluxed with stirring for forty-eight hours. The reaction mixture was cooled to room temperature and treated with an ice/ water mixture and excess concentrated hydrochloric acid. The chloroform layer was then separated, the aqueous layer extracted three times with methylene dichloride, and the combined organic extracts were extracted four times with 70% sulfuric acid. The sulfuric acid extracts were stirred with about 400 g. of an ice/water mixture, and the mixture was extracted four times with methylene dichloride. Evaporation of the combined organic extracts to dryness afiorded 6.0 g. of tan crystals which were distilled in vacuo to give 4.9 g. of 2,3-di-t-butylcyclopropenone, b.p. l17130 C./18 mm.; m.p. 62-64.5 C. (recrystallized from cold hexane).

(B) 1-anilino-2,3-di-t-butylcyclopropenylium tetrafluoroborate Asolution of 14.5 g. (0.087 mole) of 2,3-di-t-butylcyclopropenone and 19.8 g. (0.105 mole) of triethyloxonium tetrafluoroborate dissolved in 105 ml. of methylene'dichlor ide was prepared, and the solution containing 1 l eth'oxy-2,3-di-t-butylcyclopropenylium tetrafluoroborate formed in situ, was treated with 2.79 g. (0.03 mole) of aniline. The reaction mixture was stirred at room temperature for six hours after which time the mixture was filtered and the filtrate diluted with 100 ml. of anhydrous ether. The solid which separated was collected and recrystallized from a methylene dichloride/ hexane mixture to'give 6.7 g. of 1-anilino-2,3-di-t-butylcyclopropenylium tetrafluoroborate, m.p. 181-182 C.

"'Sirr iilar'ly, reaction of 3,4-methylenedioxyaniline; 3,4- ethylenedioxyaniline; '3-chloroaniline; 3-bronioaniline; 4- i'odoa'riiline; 4-fluoroaniline; 2,4,6-trimethylaniline; 3,5-dimethoxyaniline; 4-methylmercaptoaniline; or 4-(N,N- dimethylamino)aniline with 1-ethoxy-2,3-di-t-butylcyclopropenylium tetrafluoroborate in methylene dichloride affords 1- (3 ,4-methylenedioxyphenyl) amino-2,3-di-t-butylcyclopropenylium tetrafluoroborate;

1- 3,4-ethylenedioxyphenyl) amino-2,B-di-t-butylcyclopropenylium tetrafluoroborate;

1- (3-chlorophenyl) -amino-2,3 -di-t-butylcyclopropenylium tetrafluoroborate;

l- 3-bromophenyl amino-2,3-di-t-butylcyclopropenylium tetrafluoroborate;

1- (4-iodophenyl) amino-2,3-di-t-butylcyclopropenylium tetrafluoroborate;

1-(4-fluorophenyl)amino-2,3-di-t-butylcyclopropenylium tetrafluoroborate;

1- 2,4,6-trimethylphenyl) -amino-2,3-di-t-butylcyclopropenylium tetrafluoroborate;

1- (3 S-dimethoxyphenyl) amino-2,3-di-t-butylcyclopropenylium tetrafluoroborate;

1- 4-methylmercaptophenyl) amino-2,3-di-t-butylcyclo propenylium tetrafluoroborate; or

1- [4- (N,N-dirnethylamino phenyl] amino-2,3-di-t-butylcyclopropenylium tetrafluoroborate,

respectively.

EXAMPLE 2 1- l-thiosemicarbazido -2,3-di-t-butylcyclopropenylium chloride A solution of 3.32 g. (0.02 mole) of 2,3-di-t-butylcyclopropenone and 1.82 g. (0.02 mole) of thiosemicarbazide in 20 ml. of ethanolic hydrogen chloride was refluxed for seven hours, cooled to room temperature, and then diluted with a small amount of diethyl ether. The crystals which separated from the mixture on standing and cooling were collected by filtration and recrystallized from an isopropanol/ether mixture to give 2.25 g. of 1- l-thiosemicarbazido) -2,3-di-t-butylcyclopropenylium chloride, m.p. 192-194" C.

Similarly, reaction of semicarbazide with 2,3-di-tbutylcyclopropenone in the presence of methanesulfonic acid aifords ll-semicarbazido -2,3-di-t-butylcyclopropenylium methanesulfonate.

EXAMPLE 3 l-( 1 adamantylamino)-2,3-di-t-butylcyclopropenylium tetrafluoroborate was prepared by reaction of 4.53 g. (0.03 mole) of l-adamantylamine with 0.03 mole of 1- ethoxy-2,3-di-t-butylcyclopropenylium tetrafluoroborate in methylene dichloride using the procedure described above in Example 1(B). The crude product was recrystallized from isopropanol to give 4.6 g. of l-(l-adarnantylamino) -2,3-di-t-butylcyclopropenylium tetrafluoroborate, m.p. 256-258" C.

Similarly, reaction of Z-adamantylamine, N-methyl-ladamantylamine, N-ethyl-l-adamantylamine, N-methyl- 2-adamantylamine, or N-ethyl-Z-adamantylamine with l ethoxy-Z,3-di-t-butylcyclopropenylium tetrafluoroborate in methylene dichloride aflords 1-(Z-adamantylamino)-2,3-di-t-butylcyclopropenylium tetrafluoroborate,

1- (N-methyll-adamantylamino) -2,3-di-t-butylcyclopropenylium tetrafluoroborate,

1- (N-ethyll-adamantylamino -2,3 -di-t-butylcyclopropenylium tetrafluoroborate,

1- N-methyl-2-ad amantylamino -2,3di-t-butylcyclo propenylium tetrafluoroborate, or

l- (N-ethyl-2-adamantylamino) -2,3-di-t-butylcyclopropenylium tetrafluoroborate,

respectively.

EXAMPLE 4 1-phenyl-2,3-di-t-butylcyclopropenylium tetrafluoroborate To 47 ml. (0.09 mole) of a 1.91 molar solution of phenyl lithium was added a solution of 4.98 g. (0.03

mole) of 2,3-di-t-butylcyclopropenone in 30 ml. of diethyl ether while cooling the reaction mixture in an ice bath. When addition was complete, the mixture was warmed to room temperature, refluxed for two hours, and then cooled and treated with 4 ml. of water. The solid which separated was filtered off, washed with diethyl ether, and the combined filtrates were dried over magnesium sulfate and taken to dryness giving a yellow oil which was dissolved in diethyl ether and treated with a solution of tetrafluoroboric acid in glacial acetic acid/ acetic anhydride. The solid which separated was collected by filtration and recrystallized from methylene dichloride to give 3.76 g. of l-phenyl-2,3-di-t-butylcyclopropenylium tetrafluoroborate, m.p. 260262 C.

Reaction of the intermediate carbinol with hydrobromic, hydrochloric, hydroiodic, sulfuric, perchloric, ptoluenesulfonic, or methanesulfonic acids affords lphenyl-2,3-di-t-butylcyclopropenylium bromide, chloride, iodide, sulfate, perchlorate, p-toluenesulfonate, or methanesulfonate, respectively.

Similarly, reaction of 2,3-di-t-butylcyclopropenone with 3,4-methylenedioxyphenyl magnesium bromide; 3,4- ethylenedioxyphenyl magnesium bromide; 4-chlorophenyl magnesium bromide; 4-fluorophenyl magnesium bromide; 3,4,5 trimethylphenyl magnesium bromide; 2,6-dimethoxyphenyl lithium; 3-methylmercaptophenyl magnesium bromide; or 4-(N,N-dimethylamino)-phenyl magnesium bromide in diethyl ether and reaction of the resulting carbinol with hydrobromic acid affords 1- 3,4-methylenedioxyphenyl) -2, 3-di-t-butylcyclopropenylium bromide;

1-(3,4-ethylenedioxyphenyl)-2,3-di-t-butylcyclopropenylium bromide;

1- (4-chlorophenyl) -2,3-di-t-butylcyclopropenylium bromide;

1- (4-fiuorophenyl -2,3-di-t-butylcyclopropenylinm bromide;

1-(3,4,5-trimethylphenyl)-2,3-di-t-butylcyclopropenylium bromide;

1- 2,6-dimethoxyphenyl) -2,3-di-t-butylcyclopropenylium bromide;

1-(3-methylmercaptophenyl)-2,3-di-t-butylcyclopropenylium bromide; or

1- [4- (N,N-dimethylamino phenyl] -2,3-di-t-butylcyclopropenylium bromide,

respectively.

EXAMPLE 5 1 t Butylamino-2,3-di-t-butylcyclopropenylium tetrafluoroborate was prepared by reaction of 2.19 g. (0.03 mole) of t-butylamine with a solution of 0.03 mole of 1-ethoxy-2,3-di-t-butylcyclopropenylium tetrafluoroborate in methylene dichloride using the procedure described above in Example 1(B). The product was recrystallized from isopropanol to give 4.58 g. of 1-t-butylamino-2,3-dit-butylcyclopropenylium tetrafluoroborate, m.p. 205-207 C.

EXAMPLE 6 1-(2-phenyl 1 hydrazino)-2,3-di-t-butylcyclopropenylium tetrafluoroborate was prepared by reaction of 2.16 g. (0.02 mole) of phenylhydrazine with a solution of 0.02 mole of l-ethoxy-2,3-di-t-butylcyclopropenylium tetrafluoroborate in methylene dichloride using the procedure described above in Example 1(B). The product was recrystallized from isopropanol/ ether to give 3.39 g. of 1-(2-phenyl-l-hydrazino)-2,3-di-t-butylcyclopropenylium tetrafluoroborate, m.p. 141143 C.

EXAMPLE 7 1-(2-phenethyl)amino 2,3 di butylcyclopropenylium tetrafluoroborate was prepared by reaction of 2.42 g. (0.02 mole) of phenethylamine with a solution of 0.02 mole of 1-ethoxy-2,3-di-t-butylcyclopropenylium tetrafluoroborate in methylene dichloride using the procedure described above in Example 1(B). The product was recrystallized from isopropanol/diethyl ether to give 5.09 g. of 1-(2-phenethyl)amino-2,3-di-t-butylcyclopropenylium tetrafluoroborate, m.p. 12l122.5 C.

Similarly, reaction of 1-ethoxy-2,3-di-tbutylcyclopropenylium tetrafluoroborate with benzylamine;

2- (3 ,4-methylenedioxyphenyl ethylamine;

2- 3,4-ethylenedioxyphenyl ethylamine;

2- (4-chlorophenyl ethylamine;

2- (4-bromophenyl) ethylamine;

2- 4-iodophenyl) ethylamine;

2- 4-fluorophenyl) ethylamine;

2- 3 ,4,5-trimethylphenyl) ethylamine;

2- 2,6-dimethoxyphenyl ethylamine;

2- 4-methylmercaptophenyl ethylamine; or 2- [4- (N,N-dimethylamino phenyl] ethylamine in methylene dichloride afiords respectively.

EXAMPLE 8 1 dimethylamino-2,3-di-t-butylcyclopropenylium tetrafluoroborate was prepared by reaction of 4 ml. (0.06 mole) of dimethylamine dissolved in 5 ml. of cold methylene dichloride with 0.06 mole of a solution of l-ethoxy- 2,3-di-t-butylcyclopropenylium tetrafluoroborate in methylene dichloride using the procedure described above in Example 1(B). The product was recrystallized once from acetone/ether and once from isopropanol to give 2.4 g. of 1-dimethylamino-2,3-di-t-butylcyclopropenylium tetrafluoroborate, m.p. 161163 C.

EXAMPLE 9 1 amino-2,3-di-t-butylcyclopropenylium tetrafluoroborate was prepared by passing a stream of anhydrous ammonia through a solution of 0.065 mole of 1-ethoxy-2,3- di-t-butylcyclopropenylium tetrafluoroborate in methylene dichloride with stirring for forty-five minutes. The product was recrystallized once from acetone/ether and once from isopropanol to give 11.3 g. of 1-amino-2,3- di-t-butylcyclopropenylium tetrafluoroborate, m.p. 236- 238 C.

EXAMPLE 10 (A) l-(l-adamantyl) 4,4 dimethyl-Z-pentanone .was prepared by reaction of neopentyl magnesium chloride [prepared from 6.6 g. (0.025 g. atom) of magnesium and 23 g. (0.22 mole) of neopentyl chloride in ml. of ether] with 42 g. (0.20 mole) of l-adamantylacetyl chlo ride using the procedure described above in Example 1(A). The product was purified by distillation to give 43.9 g. of 1-(l-adamantyl)-4,4-dimethyl-2-pentanone, b'.p. -132 C./0.5 mm., m.p. 7880 C.

.(B) vZ -(I -adamantyI) 3 t butylcyclopropenone was prepared by brominationof 40 g. (0.16 mole) of 1-(1- adamantyl) -4,4-dimethyl-'2-pentanone with 5.5 g. (0.345 nfiole) of bromine in 240 ml. of glacial acetic acid and cycliz ationfof 488g. (0.12 mole) of the resulting 1-(1- adamantyl)-1,3-dibromo-4,4 dimethyl-2-pentanone (54 g., m.p. 111 113 C.) .With: 44 (0.2 9 mole) Of DBU all according tolthe procedure described above in Example 1(B)..Tl 1e re was thus obtained 24 g. of crude material whiclnjafiter recrystallization, gave 20.2 g. of 2-(1-adamantyll3 t-butylcyclopropenone, m.p. 133-135 C.

. (C) 1;(.l Adamantylarnino)'-2-(1-adamantyl)-3-t-butylcyclopropenyliumtetrafluoroborate: A solution of 13.4 g. (0.055" mole) of 2-(l-adamantyl)-3-t-butylcyclopropenone and 13.6 g. .(Q.071 mole) of triethyloxonium tetrafipo orate' dissolved in 100 ml. of methylene dichloride was prepareiand the solution containing 1-ethoxy-2-(1- adamantyl) 3-t butylcyclopropenylium tetrafluoroborate formed in situ was treated with 3.33 g. (0.02 mole) of l adamantylamine using the procedure described above inExample. l(B). The product was recrystallized from isopropanol to give 5.48. g. of 1-(1-adamantylamino)-2- (1. a damantyl)-3-t-butylcyclopr-openylium tetrafluoroborate, m.p. 269-273 C.

H (EXAMPLE 11 1 ('1"- adamantyl) 2,3-di-t-butylcyclopropenylium tetrafluoroborate was prepared by reaction of 6.5 g. (0.026 mole) of 2-(l-adamantyl)-3-t-butylcyclopropenone, dissolved in 50ml. of benzene, with 0.053 mole of a solution oft-butyllithium in pentane, and reaction of the resulting carbinol dissolved in 250 ml. of ether with a solution of vtetrafiuoroboric acid in glacial acetic acid/ acetic anhydride all according tothe procedure described above in Example 4. The product was recrystallized from etherito give 3.5 g. of 1-(l-adamantyl)-2,3-di-t-butylcyclopropenylium tetrafluoroborate, m.p. 286-288 C.

'Simila rlfireaction of 2-(l-adamantyl)-3-t-butylcyclopropenone with .l-adamantylmethyl magnesium bromide qr',2-(1-adarnantyl)ethyl magnesium bromide and reaction'of tl'ie'resulting carbinol with p-toluenesulfonic acid affords 1- l-adamaritylmethyl -2-( 1-adamantyl)-3-t-buty1- cyclopropenylium p-toluenesulfonate or 1-[2-(1-adamantyl ethyl] -2- 1 -adamantyl) -3-t-butylcyclopropenylium ptoluenesulfonate, respectively.

EXAMPLE 12 1-(2-phenylethyl)amino-2-( 1 adamantyl)-3-t-butylcyclopropenylium tetrafluoroborate was prepared by reaction of 2.67 g. (0.02 mole) of Z-phenethylamine with 0.02 moleof a solution of 1-ethoxy-2-(l-adamantyD-3-tbutylcyclopropenyliurn tetrafluoroborate in methylene dichlorideusing the procedure described above in Example 1(B). The-product was recrystallized from isopropanol to give 1.2 g. of 1-(2-phenylethyl)amino-2-(1-adamanty1)- 3-t-butylcyclopropenylium. tetrafluoroborate, m.p. 164- .EXAMPLE 13 i (A) .1,3-di-.(1 adamantyl)-2-propanone was prepared byreaction of l-adamantylmethyl magnesium chloride [prepared from mg. (0.017 mole) of l-adamantylmethyl chloride with 0.96 g., (0 .04 g atom) of magnesium in 25 ml. "of absolute ether] with 3.2 g. (0.015 mole) of l-adamantylacetyl chloride using the procedure described above in Example 1(A). The product was recrystallized from absolute ethanol to give 4.0 g of 1,3-di-(1-adamantyl)-2- propanone, m.p. 235249 C;

(B) 2,3-di-(1-adamantyl)cyclopropenone was prepared by bromination of 20.6 g. (0.08 mole) of 1,3-di(-adamantyl)-2-propanone dissolved in 200 ml. of glacial acetic acid-with 25 9 g.,,, (0.16 mole) of bromine in 20 ml. acidLand cycli'zation of 14.5 g. (0.03

mole) of the resulting 1,3-di-(l-adamantyl)-1,3-dibromo- 2-propanone (38.6 g., recrystallized from ethyl acetate, m.p. 199209 C.) with 15.2 g. (0.10 mole) of DBU in ml. of chloroform all according to the procedure described above in Example 1(A). The product was recrystallized once from ethyl acetate and once from ethanol to give 4.24 g. of 2,3-di-(l-adamantyl)cyclopropenone.

(C) 1 [2 (benzyloxy)ethylamino] 2,3 di (1- adamantyl)cyclopropenylium tetrafluoroborate: A solution of about 8.1 g. (0.025 mole) of 2,3-di-(1-adamantyl) cyclopropenone and 5.7 g. (0.03 mole) of triethyloxonium tetrafluoroborate dissolved in 50 ml. of methylene dichloride was prepared, and the solution containing 1- ethoxy 2,3 di-(l-adamantyl)cyclopropenylium tetrafluoroborate formed in situ was treated with 3.78 g. (0.025 mole) or 2-(benzyloxy)ethylamine using the procedure described above in Example 1(B). The product was recrystallized from isopropanol to give 6.7 g. of 1-[2- (benzyloxy)ethylamino] 2,3 di (1 adamantyl)cyclopropenylium tetrafluoroborate, m.p. 168172.5 C.

EXAMPLE 14 1 (1 adamantylamino) 2,3 di (1 adamantyl) cyclopropenylium tetrafluoroborate was prepared by reaction of 1.51 g. (0.01 mole) of l-adamantylamine with a solution containing 0.12 mole of 1-ethoxy-2,3-di (1- adamantyl)cyclopropenylium tetrafluoroborate in methylene dichloride using the procedure described above in Example 1(B). The product was recrystallized from isopropanol to give 2.1 g. of 1 (1 adamantylamino) 2,3- di-( l-adamantyl)cyclopropenylium tetrafluoroborate, m.p. 350 C.

EXAMPLE 15 1 cyclopropylamino 2,3 di (1 adamantyl)cyclopropenylium tetrafluoroborate was prepared by reaction of 0.86 g. (0.015 mole) of cyclopropylamine with a solution containing 0.015 mole of 1 ethoxy 2,3 di (1- adamantyl)cyclopropenylium tetrafluoroborate in methylene dichloride using the procedure described above in Example 1(B). The product was recrystallized from iso propanol to give 3.8 g. of 1-cyclopropylamino-2,3-di-(1- adarnantyl) cyclopropenylium tetrafluoroborate, m.p.

Similarly, reaction of 1-ethoxy-2,3-di-(1-adamantyl)- 1 (1 pyrrolidinyl) 2,3 di (1 adamantyl) cyclopropenylium tetrafluoroborate was prepared by reaction of 0.6 g. (0.008 mole) of pyrrolidine with a solution containing 0.01 mole of 1 ethoxy 2,3 di (1- adamantyl)cyclopropenylium tetrofluoroborate in methylene dichloride using the procedure described above in Ex-. ample 1(B). The product Was recrystallized from isopropanol to give 2.2 g. of 1-(1-pyrro1idinyl)-2,3-di-(1- adamantyl)cyclopropenylium tetrafluoroborate, mp. 290- Similarly, reaction of 1-ethoxy-2,3di-(l-adamantyl) cyclopropenylium tetrafluoroborate with aziridine, azetidine, piperidine, hexamethyleneimine, or morpholine in methylene dichloride affords 1-( 1-aziridino)-2,3-di-( l-adamantyl) cyclopropenylium tetrafluoroborate;

1-( l-azetidino) -2,3-di-( l-adamantyl cyclopropenylium tetrafiuoroborate;

1(1-piperidino)-2,3 -di-( l-adamantyl) cyclopropenylium tetrafluoroborate;

1-(l-hexamethyleneimino)-2,3-di-(1-adamantyl)cyclopropenylium tetrafiuoroborate; or

1-(1-morpholino)-2,3-di-(l-adamantyl)cyclopropenylium tetrafluoroborate,

respectively.

EXAMPLE 17 l ethylamino 2,3 di (1 adamantyl)cyclopropenylium tetrafiuoroborate was prepared by reaction of 0.41 g. (0.009 mole) of ethylamine with a solution containing 0.01 mole of 1-ethoxy-2,3-di-(1-adamantyl)cyclopropenylium tetrafluoroborate in methylene dichloride using the procedure described above in Example 1(B). The product was recrystallized from isopropanol to give 1.6 g. of 1-ethylamino-2,3 di (1 adamantyl)cyclopro penylium tetrafluoroborate, m.p. 242-260 C.

EXAMPLE 18 1 diethylamino 2,3 di (1 adamantyl)cyclopropenylium tetrafluoroborate was prepared by reaction of 0.64 g. (0.009 mole) of diethylamine with a solution containing 0.01 mole of 1-ethoxy-2,3-di-(l-adamantyDcyclopropenylium tetrafluoroborate in methylene dichloride using the procedure described above in Example 1(B). The product was recrystallized from isopropanol to give 1.8 g. of l-diethylamino-2,3-di (1-adamantyl)cyclopropenylium tetrafluoroborate, m.p. 240252 C.

EXAMPLE 19 1 amino 2,3 di (1 adamantyl)cyclopropenylium tetrafluoroborate was prepared by passing a stream of anhydrous ammonia into a solution containing 0.01 mole of 1 ethoxy 2,3 di (1 adamantyl) cyclopropenylium tetrafluoroborate in methylene dichloride using the procedure described above in Example 1(B). The product was recrystallized once from isopropanol and twice from ethanol to give 1.06 g. of 1-amino-2,3-di-(1-adamantyl)- cyclopropenylium tetrafluoroborate, m.p. 297312 C.

EXAMPLE 20 1 (1 thiosemicarbazido) 2,3 di (1 adamantyl) cyclopropenylium chloride was prepared by reaction of 4.83 g. (0.015 mole) of 2,3 di (1 adamantyl)cyclopropenone with 1.50 g. (0.17 mole) of thiosemicarbazide in a solution of 45 m1. of ethanolic hydrogen chloride and 15 ml. of absolute ethanol using the procedure described above in Example 2. The product was recrystallized once fmethanol and once from ethanol/ether to give 3.4 g. of 1 (1 thiosemicarbazido) 2,3 di (1 adamantyl) cyclopropenylium chloride, m.p. 231-240 C.

EXAMPLE 21 1,2,3-tri-t-butyl-2-cyclopropenyll-methylamine hydrochloride To 100 ml. of a solution containing 0.2 mole of t-butyl lithium in pentane was added a solution of 24.9 g. (0.15 mole) of 2,3-di-t-butylcyclopropenone in 150 ml. of dry benzene. The mixture was stirred at room temperature for five hours, then quenched with water, and the solid which separated was dissolved by addition of more water. Separation of the layers, extraction of the aqueous layer with diethyl ether, and evaporation of the solvent from the combined extracts aflorded an oil, which was dissolved in ether and treated with a solution of tetrafluoroboricacid in glacial acetic acid/acetic anhydride. The crystals which separated were collected by filtration and recrystallized from methylene dichloride/hexane to give 28.6 of 1,2,3- tri-t-butylcyclopropenylium tetrafluoroborate.

The latter 13.2 g., 0.04 mole) was dissolved in ml. of dry acetonitrile, 18.9 g. (0.29 mole) of potassium cyanide was added, and the mixture was heatedand stirred under reflux overnight. The mixture was then filtered, the

solid filter washed with acetonitrile and ether, and the filtrate taken to dryness giving 5.05 g. of 1,2,3-tri-t-butyl- 2-cyclopropene-l-carbonitrile as a liquid which solidified on standing (m.p. 30-32 C.).

The latter (12 g., 0.05 mole), dissolved in 60 ml. of

tetrahydrofuran, was added dropwise with stirring to a N- 2, 3di-t-butyl-2-cyclopropen-1-ylidene)-p toluenesulfonamide To a solution of 3.32 g. (0.02 mole) of 2,3-di-t-butylcyclopropenone in 20 ml. of dry methylene dichloride was added dropwise 3.94 g. (0.02 mole) of p-toluenesulfonyl isocyanate. The mixture was then stirred at room temperature for two hours and then taken to dryness in vacuo leaving a residue of white crystals which were recrystallized twice from methylene dichloride/hexane to givt 4.27 g. of N-(2,3-di-t-butyl-2-cyclopropen-1-ylidene)' p-toluenesulfonamide, m.p. 114-116 C.

I claim:

1. A compound having the formula where R and R are each t-butyl or l-adamantyl; R is 1- adamantyl-lower-alkyl, phenyl, or l-adamantyl; X- is tetrafluoroborate, and where R as phenyl is either m1- substituted or is substituted by from one to three loweralkyls.

2. 1-phenyl-2,3-di-t-butylcyclopropenylium tetrafluoroborate according to Claim 1 where R and R are each t-butyl, R is phenyl, and X" is tetrafiuoroborate.

3. 1 (1 adamantyl)-2,3-di-t-butylcyclopropenylium tetrafluoroborate according to Claim 1 where R and R are each t-butyl, R is l-adamantyl, and X is tetrafiuoroborate.

4. The process for preparing a compound according to Claim 1 having the formula Ii -LR where R and R are each t-butyl or l-adamantyl; R is l-adamantyl-lower-alkyl, phenyl, or l-adamantyl; and X 13 14 is tetrafluoroborate which comprises reacting a compound 3,466,313 9/1969 Kuntz et a1 260-6065 B having the formula 3,493,629 2/ 1970 Mitsch et a1 260-606.5 B

$ DANIEL E. WYMAN, Primary Examiner A 5 A. P. DEMERS, Assistant Examiner US. Cl. X.R.

with an organo lithium compound (R )Li or an organo '260239 B, 247, 269, 293 A, 3131, 333, 340.5, 463, 464, magnesium halide (R )MgX and treatment of the result- 468.5, 501.21, 350 R, 551 R, 552 SC, 554, 556 R,

ing carbinol with a strong acid (HX). 10 563 P, 567, 583 R, 586 R, 593, 607 R, 611 B, 617, 648, 666 M, 668 F; 424244, 282, 304, 325, 331, 335, 340, References Cited 3 UNITED STATES PATENTS 3,296,274 1/1967 Stafiej et a1 260-6065 B UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION PATENT NO. 3,839,460 DATED October 1, 1974 |NVENTOR(S) John W. Schulenberg It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 3, line 10, the structural formula on the right side should appear as:

I! R CHCCHR I I Br B Signed and Scaled this Nineteenth Day of we;

[SEAL] Aunt:

GERALD]. MOSSINGHOFF Attmlng Officer Commissioner of Patents and Trademarks 

1. A COMPOUND HAVING THE FORMULA 